• Fei Li Kuang, Fanny Legrand, Michelle Makiya, JeanAnne Ware, Lauren Wetzler, Thomas Brown, Tamika Magee, Brent Piligian, Pryscilla Yoon, Jamie H Ellis, Xiaoping Sun, Sandhya R Panch, Astin Powers, Hawwa Alao, Sheila Kumar, Martha Quezado, Li Yan, Nancy Lee, Roland Kolbeck, Paul Newbold, Mitchell Goldman, Michael P Fay, Paneez Khoury, Irina Maric, and Amy D Klion.
• From the Laboratory of Parasitic Diseases (F.L.K., F.L., M.M., J.W., L.W., T.B., T.M., B.P., P.Y., P.K., A.D.K.) and Biostatistics Research Branch (M.P.F.), National Institute of Allergy and Infectious Diseases, the Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (H.A., S.K.), and the Laboratory of Pathology, National Cancer Institute (A.P., M.Q.), National Institutes of Health (NIH), and the Departments of Laboratory Medicine (J.H.E., X.S., I.M.) and Transfusion Medicine (S.R.P.), NIH Clinical Center, Bethesda, Washington Adventist Hospital, Takoma Park (T.M.), and MedImmune (N.L., R.K.) and AstraZeneca (P.N., M.G.), Gaithersburg - all in Maryland; the Department of Veteran Affairs, Tennessee Valley Healthcare System, Chattanooga (J.H.E.); and MedImmune, South San Francisco, CA (L.Y.).
• N. Engl. J. Med. 2019 Apr 4; 380 (14): 1336-1346.

BackgroundHypereosinophilic syndrome is a group of diseases defined by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a monoclonal antibody against interleukin-5 receptor α, which is expressed on human eosinophils.MethodsIn this randomized, double-blind, placebo-controlled, phase 2 trial, we administered a series of three monthly subcutaneous injections of either benralizumab (at a dose of 30 mg) or placebo in 20 symptomatic patients who had PDGFRA-negative hypereosinophilic syndrome and an absolute eosinophil count of at least 1000 cells per cubic millimeter; all the patients were receiving stable therapy (drugs or dietary changes) for this disease. This regimen was followed by an open-label phase, during which the patient's background therapy could be tapered as tolerated, and an extension phase. The primary end point of the randomized phase was a reduction of at least 50% in the absolute eosinophil count at week 12.ResultsDuring the randomized phase, the primary end point occurred in more patients in the benralizumab group than in the placebo group (9 of 10 patients [90%] vs. 3 of 10 patients [30%], P = 0.02). During the open-label phase, clinical and hematologic responses were observed in 17 of 19 patients (89%) and were sustained for 48 weeks in 14 of 19 patients (74%); in the latter group, in 9 of 14 patients (64%), background therapies could be tapered. Bone marrow and tissue eosinophilia were also suppressed with benralizumab therapy. The most common drug-related adverse events, headache and an elevated lactate dehydrogenase level, occurred in 32% of the patients after the first dose of benralizumab and resolved within 48 hours in all patients. Other adverse events occurred with similar frequency in the two groups. Of the many potential predictors of response that were examined, only clinical disease subtype appeared to be associated with the initial response or relapse.ConclusionsIn this small phase 2 trial, patients with PDGFRA-negative hypereosinophilic syndrome who received benralizumab for 12 weeks had lower absolute eosinophil counts than those who received placebo. During the open-label phase, clinical and hematologic responses were sustained for 48 weeks in 74% of the patients. Adverse events did not limit treatment. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov numbers, NCT00001406 and NCT02130882.).Copyright © 2019 Massachusetts Medical Society.

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